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HDAC3 influences phosphorylation of STAT3 at serine 727 by interacting with PP2A

Sumihito Togi1, Shinya Kamitani, Shiho Kawakami

  • 1Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-Ku Kita 12 Nishi 6, Sapporo 060-0812, Japan.

Biochemical and Biophysical Research Communications
|January 6, 2009
PubMed

Insights

Histone deacetylase 3 (HDAC3) regulates the STAT3 signaling pathway. HDAC3 acts as a scaffold for PP2A, influencing STAT3 phosphorylation and activation, crucial in various human diseases.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Signal transducer and activator of transcription 3 (STAT3) is vital in physiological processes and implicated in human diseases.
  • STAT3 activation by cytokines and growth factors is a key signaling mechanism.

Purpose of the Study:

  • To investigate the role of histone deacetylase 3 (HDAC3) in regulating STAT3 phosphorylation and activation.
  • To elucidate the interaction between HDAC3, protein phosphatase 2A (PP2A), and STAT3.

Main Methods:

  • Treatment of HeLa cells with trichostatin A (an HDAC inhibitor) and HDAC3 siRNA.
  • Analysis of STAT3 phosphorylation at Ser727.
  • Assessment of STAT3-PP2A complex formation.
  • Evaluation of leukemia inhibitory factor (LIF)-induced STAT3 activation following HDAC3 and PP2A repression.

Main Results:

  • HDAC inhibition or HDAC3 repression enhanced STAT3 phosphorylation at Ser727.
  • HDAC3 repression restored STAT3 dephosphorylation by PP2A.
  • HDAC3 presence enhanced the formation of a STAT3-PP2A complex.
  • Repression of both HDAC3 and PP2A amplified LIF-induced STAT3 activation.

Conclusions:

  • HDAC3 functions as a scaffold protein for PP2A.
  • HDAC3 regulates the leukemia inhibitory factor/STAT3 signaling pathway via its interaction with PP2A.
  • Understanding this pathway offers insights into STAT3-mediated diseases.

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